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Dean-Mo Liu

Publications and source records attributed to Dean-Mo Liu.

14 recordsLinked to original sources

Synthesis and characterization of amphiphatic carboxymethyl-hexanoyl chitosan hydrogel: water-retention ability and drug encapsulation.

Carboxymethyl-hexanoyl chitosan (NOCHC) amphiphatic hydrogel with excellent water-absorption and water-retention abilities under neutral conditions was successfully synthesized for the first time and then employed as a carrier for delivering amphiphatic agents. NOCHC is a water-soluble chitosan derivative bearing the carboxymethyl (hydrophilic) group and the hexanoyl (hydrophobic) group, which was synthesized using N,O-carboxymethyl chitosan (NOCC) as the starting precursor. Water-absorption ability (W(c)), water-retention ability, and drug encapsulation efficiency of the NOCHC hydrogel were investigated in terms of the degree of carboxymethyl and hexanoyl substitution. It was found that the amount of moisture uptake was dependent on the relative humidity as well as degree and nature of such substitution. The hexanoyl substitution affected significantly the water-absorption ability by altering the number of water-binding sites and the state of water under low humidity and the fully swollen state, respectively. In addition, the presence of hydrophobic hexanoyl substitution significantly retards water mobility during deswelling, causing better water-retention ability. Moreover, compared with that of pristine chitosan and NOCC, the encapsulation efficiency of ibuprofen (partially hydrophobic agent) was significantly enhanced with the incorporation of the hexanoyl group. These results demonstrate that the newly developed NOCHC amphiphatic hydrogel showed enhanced water-absorption ability, water-retention ability, and amphiphatic drug encapsulation efficiency compared with NOCC and chitosan.

Calorimetry, Differential Scanning↗

Magnetic-sensitive behavior of intelligent ferrogels for controlled release of drug.

An intelligent magnetic hydrogel (ferrogel) was fabricated by mixing poly(vinyl alcohol) (PVA) hydrogels and Fe3O4 magnetic particles through freezing-thawing cycles. Although the external direct current magnetic field was applied to the ferrogel, the drug was accumulated around the ferrogel, but the accumulated drug was spurt to the environment instantly when the magnetic fields instantly switched "off". Furthermore, rapid to slow drug release can be tunable while the magnetic field was switched from "off" to "on" mode. The drug release behavior from the ferrogel is strongly dominated by the particle size of Fe3O4 under a given magnetic field. The best "magnetic-sensitive effects" are observed for the ferrogels with larger Fe3O4 particles due to its stronger saturation magnetization and smaller coercive force. Furthermore, the amount of drug release can be controlled by fine-tuning of the switching duration time (SDT) through an externally controllable on-off operation in a given magnetic field. It was demonstrated that the highest burst drug amounts and best "close" configuration of the ferrogel were observed for the SDT of 10 and 5 min, respectively. By taking these peculiar magnetic-sensitive characteristics of the novel ferrogels currently synthesized, it is highly expected to have a controllable or programmable drug release profile that can be designed for practical clinical needs.

Drug Delivery Systems↗

Study on drug release behaviour of CDHA/chitosan nanocomposites--effect of CDHA nanoparticles.

To explore the effect of nanofiller-polymer interaction on the drug release behaviour from a monolithic membrane prepared by Ca-deficient hydroxyapatite (CDHA)/chitosan nanocomposite, release kinetics was investigated in terms of different synthetic processes, i.e. in situ and ex situ routes, and various amounts of CDHA. It was found that a higher value of diffusion exponent (n) was obtained for the membranes in situ synthesized compared with those ex situ prepared. In addition, the n value of the membranes in situ synthesized increased with increasing CDHA amount, which remained in the range below 10wt.%. However, as CDHA content exceeded 30%, the n value remained constant. It indicates that the drug diffusion mechanism is altered by the CDHA-chitosan interaction which is strongly influenced by both the synthesis process and the concentration of the CDHA nanofiller in the membrane. On the other hand, a lower permeability (P) value of the membranes was observed for those prepared via the in situ process. Furthermore, P value decreased and increased with increasing CDHA amount in the range below and above 10wt.%, respectively. It demonstrates that CDHA nanofillers act either diffusion barrier or diffusion enhancer for the CDHA/chitosan membranes, which is determined by the concentration of CDHA nanofiller and the synthesis route of nanocomposite.

Biocompatible Materials↗

On the study of BSA-loaded calcium-deficient hydroxyapatite nano-carriers for controlled drug delivery.

Calcium-deficient hydroxyapatite (CDHA) nano-crystals incorporated with bovine serum albumin (BSA) to form BSA-loaded nano-carriers were synthesized via both in-situ and ex-situ processes. Amount of BSA uptake by the CDHA nano-crystals and subsequent release behaviors of the BSA-loaded nano-carriers were investigated. The amount of BSA uptake by CDHA decreases with increasing pH but a larger amount was observed in the ex-situ compared to in-situ process above pH=8.0. The release profile showed a bursting behavior for the nano-carrier prepared via the ex-situ process, which is probably due to the desorption of BSA molecules. In contrast, for the sample synthesized via the in-situ process at a higher pH level, a slower release profile without bursting behavior due to the dissolution of the BSA-incorporated CDHA crystal is seen from high solution TEM that indicates different extent of interaction between BSA and CDHA. On the other hand, for the nano-carriers prepared via the same process at lower pH level, a two-stage release profile was detected. An initial bursting release is due to the desorption of BSA from the CDHA surface, followed by a slow release as a result of the dissolution of the BSA-incorporated nano-crystals along its c-axis direction.

Animals↗

Manipulation of nanoneedle and nanosphere apatite/poly(acrylic acid) nanocomposites.

Colloidal apatitic nanosphere of 2-5 nm in diameter was synthesized in the presence of poly(acrylic acid), PAA. PAA, which has long been recognized as an inhibitor in the synthesis of hydroxyapatite, is used as a structure-directing agent for the synthesis of calcium-deficient apatite (CDHA) in this study. Experimental observation suggests a critical amount of the low-molecular-weight PAA, above which morphological evolution of CDHA nanoparticles from needle to sphere was observed. This reveals that the PAA acts as an inhibitor for the growth of CDHA crystals. Further incorporation of PAA of high molecular weight formed a highly optically transparent nanocomposite, even with the nanospherical apatite loading up to 35 wt %, suggesting no agglomeration. This was further justified through transmission electron microscopy (TEM), where the CDHA nanospheres were uniformly distributed in the PAA-CDHA nanocomposites. No interfacial crevices were visually observed, indicating a highly compatible interface between the inorganic CDHA and organic PAA phase.

Acrylic Resins↗

In-situ preparation of poly(propylene fumarate)--hydroxyapatite composite.

In-situ precipitation of hydroxyapatite (HAp) in the presence of poly(propylene fumarate) (PPF) is investigated. Amorphous calcium phosphate (ACP) precipitates in the presence of the polymer and remains in the amorphous form for a relatively long time, e.g. even after 24 h of coexistence with the mother solution. Our observations suggest that PPF interacts with the surface of the ACP particles and prevents them from transformation to crystalline hydroxyapatite. The PPF polymer seems to be more efficient in hindering the ACP to HAp transformation at higher pH conditions. From spectroscopic observations we hypothesize that the C=O bond of the PPF molecules interact with the calcium ion of the ACP particles. In case of low molecular weight PPF this interaction may lead to the incorporation of the polymer within the growing ACP particles.

Biocompatible Materials↗

Influence of the aspect ratio of bioactive nanofillers on rheological behavior of PMMA-based orthopedic materials.

In this investigation, calcium-deficient hydroxyapatite (CDHA) nanocrystals with needle-like geometry were synthesized and incorporated with Poly(methyl methacrylate), PMMA, to form CDHA-PMMA nanocomposites. Rheological behaviors of the PMMA-CDHA melting suspensions were systematically investigated in terms of solid loading and aspect ratio of the CDHA nanoparticles. The maximum solid loadings of nano-CDHA particles with aspect ratios of 7.2, 10.4, and 17 were determined to be 28, 31, and 57%, respectively. An increase in solid concentrations causes pronounced shear-thinning behavior. This result suggests that a strong interaction, including Van der Waals attraction and mechanical interlocking, between the nano-CDHA particles makes the nanocomposite mixture more non-Newtonian. Furthermore, it was found that packing efficiency and yield strength in the suspension were strongly influenced by the aspect ratio, especially above the critical value of 8.8. The obtained critical aspect ratio and solid content provide not only appropriate design in the PMMA-CDHA polymeric suspension for fabrication process but also optimal conditions for the fabrication of orthopedic devices via injection molding or extrusion.

Biocompatible Materials↗

Phase development and structural characterization of calcium phosphate ceramics-polyacrylic acid nanocomposites at room temperature in water-methanol mixtures.

Calcium phosphate ceramics (CPCs) were prepared via an in-situ formation in the presence of polyacrylic acid (PAA) polymer under water-methanol (WM) mixture at room temperature. The PAA polymer was employed as both structure-directing agent and crystallization retardant to manipulate the development of resulting CPCs nano-crystallites which are observed to show a core-shell configuration with a thin layer of PAA molecules. A resulting phase evolution map with respect to the developing phases of calcium-deficient hydroxyapatite (CDHA), beta-tricalcium phosphate (beta-TCP), and an intermediate amorphous calcium phoshate (ACP) that were structurally and spectroscopically identified, was constructed in terms of fractions of water-to-methanol proportions and concentration of PAA. It is found that for the solutions in both water-rich and methanol-rich regions, pure CDHA and beta-TCP instead of intermediate ACP phase can be developed irrespective of the concentration of PAA, respectively. For conditions in between, i.e., with methanol fractions of 15%-90%, ACP appeared only when the PAA fell in a limited concentration range.

Acrylic Resins↗

Synthesis and characterization of needlelike apatitic nanocomposite with controlled aspect ratios.

Calcium-deficient apatitic (cd-HA) crystals with core-shell nanostructure with needlelike shape, 5-10nm in diameter and 20-80nm in length, were prepared via an in situ formation in the presence of polyacrylic acid (PAA) under aqueous solution of different pH values, ranging from 9 to 11. Nanostructure of the resulting crystals showing a core-shell configuration with a thin layer of PAA shell of about 1nm thickness was investigated. Aspect ratio (AR) of the needlelike composite was found to depend on the concentration of the PAA and solution pH. At lower solution pH, crystal growth was inhibited, i.e., leading to a decreased AR, with increase of PAA concentration, while an increased AR was detected at higher solution pH, suggesting a preferential growth of the cd-HA nanocrystals. Mechanism of such preferential growth was tentatively proposed and is suggested to correct PAA adsorption along the long axis of the needlelike nanoparticles.

Acrylic Resins↗

Sol-gel hydroxyapatite coatings on stainless steel substrates.

Thin film hydroxyapatite deposits onto sandblasted 316L stainless steel substrates were prepared using water-based sol-gel technique recently developed in our lab. The coatings were annealed in air at 375 degrees C, 400 degrees C, and 500 degrees C. Phase formation, surface morphology, interfacial microstructure, and interfacial bonding strength of the coatings were investigated. Apatitic structure developed within the coatings while annealing at temperatures > or = 400 degrees C, while those heat-treated at 375 degrees C showed poor crystallinity. The coatings were dense and firmly attached to the underlying substrates, reaching an average bonding strength (as determined through the pull-out test) of 44 MPa. Nano-porous structure was found for the coatings annealed at 500 degrees C, believed to result from grain growth, and causing a slight decrease in the bonding strength. Surface microcracking, although not extensive, occurred after annealing at temperatures > or = 400 degrees C, and was linked to non-uniform thickness of the coating due to roughness of the substrate. A contraction of the coatings as a result of sintering, and phase transition from amorphous (or poor crystalline) to reasonably good crystalline apatite, may be responsible for the loss of structural integrity of the thicker sections of the coatings. It seems quite promising that a dense and adhesive apatite coating can be achieved through water-based sol gel technology after short-term annealing at around 400 degrees C in air.

Bone Substitutes↗

Aging effect on the phase evolution of water-based sol-gel hydroxyapatite.

In a number of recent reports on the synthesis of sol-gel hydroxyapatite, aging of the precursor solution has been found to be critical in developing an apatitic phase. Critical aging time is required to complete reaction between Ca and P molecular precursors to form a desired intermediate complex that permits a further transformation to apatite phase under appropriate thermal treatment. In this investigation, we employed a water-based sol-gel process recently developed to fabricate hydroxyapatite at relatively low temperatures. The aging effect on apatite formation was systematically studied in terms of aging time and temperature. Experimental results show that the aging time is considerably reduced as aging temperature rises. Long-term thermal aging was unfavorable for apatite formation. The optimal aging parameters for apatite formation were experimentally determined, which was further consolidated into a phase evolution map. Aging kinetic was investigated by monitoring the variation of solution pH, following the determination of an apparent activation energy, which has a value as high as 10.35 kcal/mol, for the chemical reaction occurring upon aging. Optimal solution chemistry was elucidated based on the corresponding phase evolution map.

Biocompatible Materials↗

Structural evolution of sol-gel-derived hydroxyapatite.

Structural evolution upon transformation of sol to gel, and gel to final ceramic during the synthesis of hydroxyapatite is investigated using Fourier transform infrared (FTIR) analysis, X-ray diffraction (XRD), thermal behavior (DTA and TGA), and electron microscopy examination (SEM/TEM). The sol was first thermally aged at 45 C for various time periods up to 120 min. The colloidal sol, which may have an oligomeric structure, was relatively stable against coagulation. Upon drying, the sol particles consolidated into dry gel through van der Waals attraction, and showed X-ray amorphous phosphate structure. The solid gels showed a particulate microstructure, composed of primary particles of about 8-10 nm in diameter. The amorphous gel transformed into crystalline apatite at temperatures > 300 C. The calcined gels showed a nano-scale microstructure, with grains of 20-50 nm in diameter. Through an appropriate heat treatment between 300 and 400d degrees C. the apatite prepared using current process exhibits a nano-scale, low-crystallinity, carbonated apatitic structure, which closely resembles that of human bone apatite.

Biocompatible Materials↗

Influence of apatite seeds on the synthesis of calcium phosphate cement.

This preliminary study explores the seeding effect (using crystalline hydroxyapatite particles) on the setting time, compressive strength, phase evolution, and microstructure of calcium phosphate cements (CPC) based on monocalcium phosphate monohydrate and calcium hydroxide. Experimental results showed that the setting time varies from 5 to about 30 min, as the seed concentration increased from 0 to 20 wt%. The compressive strength of CPC increased from 4 to 17 MPa, followed by decrease to 12 MPa, for the same range of seeds content. The CPC transformed to predominantly apatitic structure within 24 h for all the samples, with or without the seeds. However, increase of the seed concentration improved the final crystallinity of the apatite phase, suggesting nucleation and growth effects during precipitation of CPC from the precursor solution. The microstructure of the resulting apatitic cement showed a change from essentially featureless (or glass-like) to thin, elongated plate-like morphology, as seeds concentration increased. Correlation between microstructural evolution and corresponding compressive strength of seeded CPC is investigated.

Apatites↗

Effect of hydroxyapatite nanoparticles on ibuprofen release from carboxymethyl-hexanoyl chitosan/O-hexanoyl chitosan hydrogel.

In order to explore the effect of nanofiller on the regulation of the drug release behavior from microsphere-embedded hydrogel prepared by carboxymethyl-hexanoyl chitosan (HNOCC) and O-hexanoyl chitosan (OHC), the release kinetics was investigated in terms of various amounts of calcium-deficient hydroxyapatite (CDHA) nanoparticles incorporated. HNOCC is a novel chitosan-based hydrophilic matrix with a burst release profile in a highly swollen state. The drug release kinetics of the HNOCC hydrogel can be regulated by incorporation of well-dispersed CDHA nanoparticles. It was found that the release duration of ibuprofen (IBU) from HNOCC was prolonged with increasing amounts of CDHA which acts as a crosslink agent and diffusion barrier. On the contrary, the release duration of the IBU from OHC (hydrophobic phase) was shortened through increasing the CDHA amount over 5%, which is due to the hydrophilic nature of the CDHA nanoparticles destroying the intermolecular hydrophobic interaction and accelerating OHC degradation. Thus, water accessibility and molecular relaxation were enhanced, resulting in a higher release rate. In addition, sustained and sequential release behavior was achieved by embedding the OHC microspheres (hydrophobic phase) into the HNOCC (hydrophilic phase) matrix, which could significantly prolong the release duration of the HNOCC drug-loaded implant.

Animals↗